A 73-gene proliferative transcriptomic signature predicts uterine serous carcinoma patient survival and response to primary therapy.

OBJECTIVES: To develop a transcriptomic signature capable of predicting overall survival (OS) for uterine serous carcinoma (USC). METHODS: RNAseq data for 58 USC patients were obtained from TCGA. Expression of 73 candidate genes was measured for 67 Augusta University (AU) samples using NanoString technology. RESULTS: Analysis of the TCGA RNAseq data identified 73 genes that individually predict prognosis for USC patients and an elastic net model with all 73 genes (USC73) distinguishes a good OS group with low USC73 score from a poor OS group with high USC73 score (5-year OS = 83.3% and 13.3% respectively, HR = 40.1; p = 3 × 10-8). This finding was validated in the independent AU cohort (HR = 4.3; p = 0.0004). The poor prognosis group with high USC73 score consists of 37.9% and 32.8% of patients in the TCGA and AU cohort respectively. USC73 score and pathologic stage independently contribute to OS and together provide the best prognostic value. Early stage, low USC73 patients have the best prognosis (5-year OS = 85.1% in the combined dataset), while advanced stage, high USC73 patients have the worst prognosis (5-year OS = 6.4%, HR = 30.5, p = 1.2 × 10-12). Consistent with the observed poor survival, primary cell cultures from high USC73 patients had higher proliferation rate and cell cycle progression; and high USC73 patients had lower rates of complete response to standard therapy. CONCLUSIONS: The USC73 transcriptomic signature and stage independently predict OS of USC patients and the best prediction is achieved using USC73 and stage. USC73 may also serve as a therapeutic biomarker to guide patient care.

Head and Neck Sarcomas: A Review of Clinical and Imaging Findings Based on the 2013 World Health Organization Classification.

OBJECTIVE: Head and neck sarcomas are a complex, heterogeneous group of tumors that present a diagnostic challenge to radiologists because they have many overlapping imaging features. The purpose of this article is to review the imaging and clinical features and highlight distinguishing features of head and neck sarcomas. CONCLUSION: An understanding of characteristic imaging and clinical features of head and neck sarcomas is important for the radiologist to narrow the differential diagnosis and help guide management.

Egg-and-Banana Sign: A Novel Diagnostic CT Marker for Pulmonary Hypertension.

OBJECTIVE: The purpose of this study was to retrospectively determine whether the egg-and-banana sign, defined as the visualization of the main pulmonary artery (PA) at the level of the aortic arch, is a sensitive and specific diagnostic marker for pulmonary hypertension. MATERIALS AND METHODS: A total of 186 patients who, between January 2014 and July 2017, received right heart catheterizations and underwent CT studies that included the aortic arch within 140 days of catheterization were evaluated in this retrospective study. Of these patients, 127 had pulmonary hypertension (PH), and 59 who did not have PH served as control subjects. Two blinded radiologists reviewed each study for the egg-and-banana sign. The diameters of the main PA and ascending aorta were also measured. Contingency tables, ROC curves, and a t test were used for statistical analysis. RESULTS: The egg-and-banana sign was associated with a higher mean PA pressure, a higher ratio of the diameter of the PA to the diameter of the ascending aorta (Ao) (hereafter referred to as the "PA-to-Ao ratio"), and a larger PA diameter (p < 0.006). It had a specificity of 85% and a positive predictive value of 85%. When the egg-and-banana sign was used in combination with a main PA diameter larger than 29 mm and a PA-to-Ao ratio greater than 1, its specificity increased to 91% and 93%, respectively. When considered as individual markers, the PA diameter had a high sensitivity (80%; AUC value, 0.74) and the PA-to-Ao ratio had a high specificity (81%; AUC value, 0.73) for PH. Moderate correlations were noted between PA pressure and PA diameter (r = 0.37) and between PA pressure and PA-to-Ao ratio (r = 0.43). CONCLUSION: The egg-and-banana sign has a high specificity and PPV for PH. Specificity increased when the sign was used in combination with other classic CT markers.

A retained secretory signal peptide mediates high density lipoprotein (HDL) assembly and function of haptoglobin-related protein.

Haptoglobin-related protein (Hpr) is a component of a minor subspecies of high density lipoproteins (HDL) that function in innate immunity. Here we show that assembly of Hpr into HDL is mediated by its retained N-terminal signal peptide, an unusual feature for a secreted protein and the major difference between Hpr and the soluble acute phase protein haptoglobin (Hp). The 18-amino acid signal peptide is necessary for binding to HDL and interacts directly with the hydrocarbon region of lipids. Utilizing model liposomes, we show that the rate of assembly and steady-state distribution of Hpr in lipid particles is mediated by the physical property of lipid fluidity. Dye release assays reveal that Hpr interacts more rapidly with fluid liposomes. Conversely, steady-state binding assays indicate that more rigid lipid compositions stabilize Hpr association. Lipid association also plays a role in facilitating hemoglobin binding by Hpr. Our data may offer an explanation for the distinct distribution of Hpr among HDL subspecies. Rather than protein-protein interactions mediating localization, direct interaction with phospholipids and sensitivity to lipid fluidity may be sufficient for localization of Hpr and may represent a mechanism of HDL subspeciation.

Persistent Lobar Atelectasis in a Patient With Chronic Hoarseness.

A 61-year-old woman presented for outpatient evaluation of a 1-week history of fever and upper respiratory symptoms. She denied tobacco use, weight loss, hemoptysis, chronic cough, or recent travel and was in otherwise good health. Her medical history was insignificant except for her chronic hoarseness from a prior laryngeal disease. She denied any worsening hoarseness or any other vocal changes. She did report a positive family history of squamous cell lung cancer in her father.